Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-02

AUTHORS

Sun-Gou Ji, Brian D Juran, Sören Mucha, Trine Folseraas, Luke Jostins, Espen Melum, Natsuhiko Kumasaka, Elizabeth J Atkinson, Erik M Schlicht, Jimmy Z Liu, Tejas Shah, Javier Gutierrez-Achury, Kirsten M Boberg, Annika Bergquist, Severine Vermeire, Bertus Eksteen, Peter R Durie, Martti Farkkila, Tobias Müller, Christoph Schramm, Martina Sterneck, Tobias J Weismüller, Daniel N Gotthardt, David Ellinghaus, Felix Braun, Andreas Teufel, Mattias Laudes, Wolfgang Lieb, Gunnar Jacobs, Ulrich Beuers, Rinse K Weersma, Cisca Wijmenga, Hanns-Ulrich Marschall, Piotr Milkiewicz, Albert Pares, Kimmo Kontula, Olivier Chazouillères, Pietro Invernizzi, Elizabeth Goode, Kelly Spiess, Carmel Moore, Jennifer Sambrook, Willem H Ouwehand, David J Roberts, John Danesh, Annarosa Floreani, Aliya F Gulamhusein, John E Eaton, Stefan Schreiber, Catalina Coltescu, Christopher L Bowlus, Velimir A Luketic, Joseph A Odin, Kapil B Chopra, Kris V Kowdley, Naga Chalasani, Michael P Manns, Brijesh Srivastava, George Mells, Richard N Sandford, Graeme Alexander, Daniel J Gaffney, Roger W Chapman, Gideon M Hirschfield, Mariza de Andrade, The UK-PSC Consortium, The International IBD Genetics Consortium, The International PSC Study Group, Simon M Rushbrook, Andre Franke, Tom H Karlsen, Konstantinos N Lazaridis, Carl A Anderson

ABSTRACT

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC. More... »

PAGES

269-273

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3745

    DOI

    http://dx.doi.org/10.1038/ng.3745

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001400355

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27992413


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